Fronto-limbic Connectivity in Adolescents with MDD

描述（由申请人提供）：目标/假设：青春期是大脑成熟和神经元连接完善的重要时期，也是重度抑郁症（MDD）患病率显著增加的时期。额边缘神经网络介导情绪处理，并涉及MDD的病理生理。我们的首要假设是，重度抑郁症是由额边缘神经回路发育异常引起的。神经成像方法的最新进展已经允许测量神经连接的强度，或“连通性”。例如，扩散张量成像（diffusion tensor imaging， DTI）可以测量“结构连通性”，静息状态功能磁共振成像（resting-state functional magnetic resonance imaging, rsfMRI）可以测量“功能连通性”。在使用这些方法对14名重度抑郁症青少年和14名健康对照者进行的初步研究中，我们发现抑郁症组亚属前扣带皮层和其他关键额边缘区域之间的结构和功能连通性都有所减少。这些发现的结论是有限的，因为与抑郁症组的小样本量和药物暴露有关的混淆。为了更好地描述抑郁症青少年额边缘网络的发育异常，我们现在建议进行多模式神经影像学调查，以检查更大的治疗初期样本的结构和功能连接。建议的方法：将从明尼苏达大学和社区的临床环境中招募30名年龄在13-17岁的具有家族性、青春期发病、中重度重度重度重度抑郁症的青少年和30名性别、利手性、社会经济地位和智商相匹配的健康对照。评估将包括K-SADS-PL、BDI、CDRS和WASI。神经成像扫描将在UMN研究专用的西门子3T扫描仪上获得。将收集结构、扩散张量和静息状态功能图像。结构连接数据将使用体素比较和概率轨迹图进行分析。功能连接将使用基于种子的方法进行分析。讨论/意义：抑郁症青少年额边缘神经网络异常连通性的证明将有助于我们理解青少年重度抑郁症的神经发育机制。该项目的数据集将为未来的纵向研究提供基础：(1)描述重度抑郁症患者的神经发育轨迹，(2)确定治疗反应的预测因子，(3)检查治疗对神经回路的影响，以及(4)研究青少年重度抑郁症神经异常发育的遗传和环境基础。通过识别儿童抑郁症背后的神经发育异常，我们的希望是告知干预措施的发展，将改变消极的轨迹。

DESCRIPTION (provided by applicant): Objective/Hypothesis: Adolescence is a time period notable for significant brain maturation and refinement of neuronal connections, and also for a marked increase in prevalence of Major Depressive Disorder (MDD). Fronto-limbic neural networks mediate emotional processing and are implicated in the pathophysiology of MDD. Our over-arching hypothesis is that MDD results from abnormal development of fronto-limbic neural circuitry. Recent advances in neuroimaging methodology have allowed for measuring the strength of neural connections, or "connectivity". For instance, diffusion tensor imaging (DTI) can be used to measure "structural connectivity", and resting-state functional magnetic resonance imaging (rsfMRI) can be used to measure "functional connectivity". In a preliminary study using these methods in 14 adolescents with MDD and 14 healthy comparison subjects, we identified a reduction in both structural and functional connectivity between the subgenual anterior cingulate cortex and other key fronto-limbic areas in the depressed group. Conclusions from these findings are limited due to confounds related to small sample size and medication exposure in the depressed group. In order to better characterize the developmental abnormalities in fronto-limbic networks in depressed adolescents, we now propose to conduct a multi-modal neuroimaging investigation to examine structural and functional connectivity in a larger, treatment-naive sample. Proposed Methods: 30 adolescents aged 13-17 with familial, adolescent onset, moderate-severe MDD and 30 healthy comparisons matched for sex, handedness, SES and IQ will be recruited from clinical settings at the University of Minnesota and the community. Assessment will include the K-SADS-PL, BDI, CDRS, and WASI. Neuorimaging scans will be obtained at a research-dedicated Siemens 3T scanner at UMN. Structural, diffusion tensor, and resting-state functional images will be collected. Structural connectivity data will be analyzed using a voxel-wise comparison and also using probabilistic tractography. Functional connectivity will be analyzed using a seed-based approach. Discussion/Significance: Demonstration of abnormal connectivity within fronto-limbic neural networks in depressed teens will inform our understanding of the neurodevelopmental mechanisms of adolescent MDD. The dataset from the proposed project will provide the foundation for future longitudinal investigations to (1) delineate trajectories of neural development in individuals with MDD, (2) identify predictors for treatment response, (3) examine the impact of treatment on neural circuitry, and (4) investigate the genetic and environmental underpinnings of abnormal neural development in adolescent MDD. By identifying neurodevelopmental abnormalities that underlie the pediatric depression, our hope is to inform the development of interventions that will alter negative trajectories. PUBLIC HEALTH RELEVANCE: Neurobiological research is urgently needed to address the significant public health burden posed by Major Depressive Disorder (MDD). This illness frequently begins in adolescence. Since early interventions hold promise for impacting malleable systems and altering trajectories, advancement in the neurodevelopmental biology of MDD during adolescence is especially critical.